Clinical and molecular characteristics of newly reported mitochondrial disease entity caused by biallelic PARS2 mutations
Clinical and molecular characteristics of newly reported mitochondrial disease entity caused by biallelic PARS2 mutations
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DOI：
10.1038/s10038-017-0401-z
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Pronicka, Ewa
中科院分区：
文献类型：
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作者：
Ciara, Elzbieta;Rokicki, Dariusz;Pronicka, Ewa
参与线粒体蛋白质合成的19种线粒体氨酰-tRNA合成酶（mt-aaRS）中的大多数已经与特定实体相关联，其中一个例外是PARS 2突变，其致病意义尚未最终验证。本研究的目的是描述PARS 2相关的表型，三个双等位基因PARS 2突变的兄弟姐妹从出生起就表现为婴儿痉挛、继发性小头畸形和类似的面部畸形。智力发育严重受损，言语缺失，没有眼神交流。在儿童期末期出现扩张型心肌病和多器官衰竭，丙戊酸盐给药引发线粒体功能障碍，脑MRI显示额叶皮质和皮质下进行性体积丢失，皮质沟和侧脑室前角增宽。胼胝体发育不全和进行性脱髓鞘是额外的发现。在三个已经报道的PARS 2患者中观察到了类似的大脑特征，并且与其他mt-aaRS缺陷相比，似乎对该缺陷具有特异性（DARS 2、EARS 2、IARS 2和RARS 2）.在来自具有PARS 2突变的三个不同种族的家族的六名患者中，表型和Alpers样脑MRI变化的惊人相似性以额叶脑体积损失（FCVL-AS）为主，有理由将该病症区分为新的疾病实体。
Most of the 19 mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) involved in mitochondrial protein synthesis are already linked to specific entities, one of the exceptions being PARS2 mutations for which pathogenic significance is not finally validated. The aim of the study was to characterize the PARS2- related phenotype.Three siblings with biallelic PARS2 mutations presented from birth with infantile spasms, secondary microcephaly, and similar facial dysmorphy. Mental development was deeply impaired with speech absence and no eye contact. A dilated cardiomyopathy and multiorgan failure developed in childhood at the terminal stage, together with mitochondrial dysfunction triggered by valproate administration.Brain MRI showed progressive volume loss of the frontal lobes, both cortical and subcortical, with widening of the cortical sulci and frontal horns of the lateral ventricles. Hypoplasia of the corpus callosum and progressive demyelination were additional findings. Similar brain features were seen in three already reported PARS2 patients and seemed specific for this defect when compared with other mt-aaRSs defects (DARS2, EARS2, IARS2, and RARS2).Striking resemblance of the phenotype and Alpers-like brain MRI changes with predominance of frontal cerebral volume loss (FCVL-AS) in six patients from three families of different ethnicity with PARS2 mutations, justifies to distinguish the condition as a new disease entity.